2. Causes of Hyponatremia in
Children
Hypovolemic
Normovolemic hyponatremia (DM)
Intestinal salt loss
Diarrheal dehydration
Vomiting,gastric suction
Fistulae
Laxative abuse
Transcutaneous salt loss
Cystic fibrosis
Endurance sport
Renal sodium loss
Mineralocorticoid defiency (or resistance)
Diuretics
Salt-wasting renal failure
Salt-wasting tubulopathies
Cerebral salt wasting
Perioperative
Third space losses (burns, septic shock,
sergery)
Normovolemic or Hypervolemic
Increased body water
Parenteral hypotonic solutions
Tap water enemas
Compulsive water drinking
Nonosmolar release of antidiuretic hormone
Cardiac failure
Severe liver disease (mostly cirrhosis)
Nephrotic syndrom
Glucocorticoid deficiebcy
Drugs causing renal water retention
(hypotyroidism)
Syndrome of inappropriate antidiuresis
Classic syndrome of inappropriate secretion of
antidiuretic hormone
Hereditary nephrogenic syndrome of
inappropriate antidiuresis
Reduced renal water loss
Chronic renal failure
Oliguric acute renal failurei
Мario G.Dianchetti, Alberto Bettinelli, 2008
3.
4. Objectives
review the tubular handling of the major electrolytes
(Na⁺, K⁺, Ca⁺², Mg⁺²)
understand the role of the tubular cells involved in
the handling of electrolytes:
1. Proximal tubular cell (PT)
2. Thick ascending limp cell (TAL)
3. Distal tubular cell (DT)
4. Collecting dust cell (CD)
7. NA (Sodium)
In adults more than 99% of filtered Na⁺ is reabsorbed
in the tubules
20-30% reabsorbed in the thick ascending limb (TAL)
5-10% is reabsorbed in the distal tubule (DT)
5-10% is reabsorbed in the collecting dust (CD)
8. Sodium: TAL
Na⁺ and cloride (Cl¯) enter the cell via the apical
electroneutral Na⁺-K⁺-2Cl¯ cotransporter (NKCC2)
This is electrochemically favorable because of low
intracellular Cl¯ and K⁺ levels
The low intracellular K⁺ levels are maintained by the
ROMK channel
Low Cl¯ levels are maintained by CIC-Kb channel
9.
10. Sodium: DT
Sodium in the DT is reabsorbed at the apical
membrane via the thiazide sensitive
Na⁺- Cl¯ contransporter (TSC)
At the basolateral surface Na⁺ and Ca⁺² compete for
reabsorption in the DT
The more Na arrives at the DCT the less Ca is
reabsorbed and the greater the degree of
hypercalciuria
11.
12. Sodium: CD
Na⁺ is reabsorbed through ENaC located on the
apical membrane of principal cells
ENaC activity and density is under the control of
aldosterone
These channels are responsible for the final
modification of sodium excretion in response to oral
intake
Each molecule of Na reabsorbed requires the
secretion of K⁺ (or H⁺) ion
13.
14. Potasium
Unlike Na⁺, K⁺ is both reabsorbed and secreted in the tubules
25% is reabsorbed in the TAL via Na⁺-K⁺-2Cl¯ transported
By the time the filtrate reached the DCT only 10% of filtered
K+ remains
15. Potassium - Secretion
In the collecting dust K⁺ is secreted and not reabsorbed
The basolateral Na⁺/K⁺ATPase activity drives the whole
process
The magnitude of K⁺ secretion depends on: availability
of Na⁺(electrochemical gradient), serum K⁺,
aldosterone, urine flow rate
16.
17. Calcium
98-99% Ca⁺² reabsorbed in the tubules
20% is reabsorbed in the TAL, which is driven by the
large positive transepthelial voltage difference
This is in part regulated by the calcium sensing
receptor (CaSR)
18. Calcium: DT
5 – 10% of Ca⁺² is reabsorbed in the DT
In contrast to the proximal tubule and TAL most of the
Ca reabsorbed in the DT is transcellular (TRPV-5)
19. Magnesium
Around 95% of filtered Mg is reabsorbed in the tubules
70-75% in the TAL
10% in the DT
20. Magnesium: TAL
Mg⁺² absorption is passive and paracellular
The main driving force is the transepithelial voltage
gradient
The permeability of the paracellular pathway is
determined by proteins such as paracellin-1 (claudin 16)
21. Magnesium: DT
Responsible for 10% of Mg⁺² reabsorption
Recent evidence suggests that the TSC interacts with
the TRPM6 (Mg⁺² transporter) in the DT and causes
Mg⁺² wasting
22.
23. Bartter/Gitelman Syndrome
Both characterized by renal salt wasting,
hypokalemia, and metabolic alkalosis
Bartter syndrome (BS) is associated with
hypercalciuria and normal serum magnesium levels
Gitelman syndrome typically associated with
hypocalciuria and hypomagnesemia
24. Bartter/Gitelman Syndrome
The different phenotypes are the result of genetic
defects causing impaired channel activity at different
locations within the nephron
Bartter syndrome = Defective TAL
Gitelman syndrome = Defective DT
27. Clinical
Neonatal Bartter Syndrome
(BS type I, II, IV)
Neonatal or fetal presentation
Severe polyhydramnios
Prematurity (usually 27-35 weeks)
Severe intravascular volume depletion/dehydratation
Polyuria
Growth retardation
Rarely Deafness
28. Clinical
Classic Bartter Syndrome (Type III)
Usually presents under the age of 6
Salt craving
Polyuria/dehydration
Emesis/constipation
Failure to thrive
Rarely periodic paralysis/rhabdomyolysis
29. Clinical
Gitelman Syndrome
May present anytime but usually in adolescence or early
adulthood
Muscle weakness/spasms/tetany
Paresthesias
Salt craving
Polydipsia/polyuria
Joint pains (chondrocalcinosis)
Rarely cardiac arrhythmias
Rarely periodic paralysis/ rhabdomyolysis
30. Bartter syndrome
The renin - aldosterone system is activated in an
attempt to counteract the volume/Na+ loss
This stimulating excess K⁺ and H⁺ excretion in the
collecting dust
In the BS the profound hypovolemia and hypokalemia
further stimulate excessive prostaglandin E2
production
This amplifies to the defect in Na⁺ and H2O
reabsorption
31.
32. Hypercalciuria in Bartter syndrome
The potential difference maintained across the TAL is
lost and therefore calcium is not able to be reabsorbed
paracellularly
There is decreased calcium reabsorption in the DT
because it normally competes with sodium which is
now more abundant
33. Gitelman syndrome and
hypocalciuria
Decreased entry of Cl¯ through the TSC and leakage
of Cl¯ out the basolateral membrane hyperpolarizes
the membrane and opens TRPV-5 channels
Na⁺ and Ca⁺² competes for reabsorption in the DT.
Less Na reabsorption promotes greater Ca
reabsorption
34. Pseudohypoaldosteronism
Type I (cortical collecting tubule)
Autosomal recessive: reduced sodium channel activity
Autosomal dominant: mutations in gene for
mineralocorticoid receptor, phenotype mild and
transient
Type II (familial hyperkalemic hypertension or Gordon
syndrom)